OBJECTIVES: Depression and weight loss are common problems in older nursing facility (NF) residents. Mirtazapine is among the interventions clinicians use to prevent weight loss in depressed, frail elderly because it has been reported to be associated with weight gain. Nevertheless, limited data in weight outcomes of depressed NF residents are available. Our objective was to examine changes in weight associated with the use of mirtazapine compared to other non-TCA antidepressant therapies in the NF population. METHODS: A retrospective chart review was conducted for 189 NF residents with new single-antidepressant treatment regimens with at least 6 months of post-treatment weight data. OLS regression was performed to assess weight change and percentage weight change at three months and six months. Mirtazapine-treated subjects served as the controlled group (n=27). Other factors affecting weight were included as explanatory variables, such as gender, age, co-morbidities, baseline weight and relative therapeutic dose. RESULTS: We found no statistical significant differences in weight change at three months and at six months between mirtazapine and all non-TCA antidepressants except fluoxetine which was associated with a gain of four pounds relative to mirtazapine at three months (p=0.0482). A hypertension diagnosis was associated with significant weight gains at 3 months (2.2 lbs., p=0.0439 or +1.7%, p=0.0361) and at 6 months (3.99 lbs., p=0.0051 or +3.1%, p=0.0048). A diagnosis of diabetes was associated with weight loss at 6 month (-3.6 lbs., p=0.0370; -3.1%, p=0.0187). Baseline weight was associated with increased weight loss in women at 6 months (-0.089 lb (per pound baseline), p=0.0388). CONCLUSIONS: With the exception of fluoxetine, our sample of NF residents showed that weight gains with mirtazapine were not statistically different from other non-TCA antidepressants once factors such as baseline weight, gender, dose and co-morbid diagnoses are controlled for statistically.